A controlled prospective randomized trial of adjuvant chemoradiotherapy following radical cystectomy in advanced high risk bladder cancer

Abstract

5082 Background: High risk locally advanced bladder cancer patients experienced low survival rates, high local recurrence and high rate of distant metastasis. Postoperative radiotherapy (PORT) improved local control and survival, yet it did not affect distant metastasis. Methods: A prospective randomized trial was performed at NCI, Cairo, Egypt including 146 patients in 2 arms. Patients who underwent radical cystectomy and pelvic lymphadenectomy had to have one or more of the following: stage P3b or P4a, G3 or involved lymphadenopathy. Arm I (74 patients) received PORT 45 Gy/30 fractions/3 weeks. Arm II (72 patients) received 2 courses of adjuvant chemotherapy (Gemcitabine 1 gm/m2 D1 and D8 and cisplatin 70 mg/m2 D2), same PORT regimen followed by another 2 courses of Gemcitabine-cisplatin. Results: Chemotherapy and radiation were tolerated with grade 1/2 toxicities. Delayed toxicity was comparable in both arms. The 45-month DFS was 51 ± 12 % in the whole group. This was affected significantly by performance status (p = 0.0001), pathological stage (p = 0.0099), nodal involvement (p = 0.004) and number of risk factors (p = 0.16). Though there was improvement of 45-month DFS from 28 ± 20% in PORT group to 70 ± 6 % in chemoradiotherapy group, yet it did not reach to the level of statistical significance (p = 0.18). Patients having one risk factor, G3 or no nodal involvement in arm II experienced better DFS than those in arm I (p = 0.17, 0.11 and 0.17 respectively). Distant metastasis-free survival (DMF) rate increased with the addition of chemotherapy from 29±21% to 75±6%. This effect was intensified in patients having one risk factor, grade 3 and negative nodes. Conclusions: Adjuvant chemoradiotherapy using Gemcitabine-cisplatin and PORT was tolerable. There was DFS improvement and higher DMF rates with the addition of chemotherapy to PORT (not statistically significant yet). Patients with one risk factor, G3 or no nodal involvement seemed to benefit more from the added chemotherapy. No significant financial relationships to disclose.